Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression |
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| Authors: | Tzi-Peng Yang Hui-Ling Chiou Ming-Chei Maa Chau-Jong Wang |
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| Affiliation: | 1. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan;2. Institute of Medical Science, China Medical University, Taichung 40402, Taiwan;3. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kauo N. Road, Taichung 40402, Taiwan;1. Department of Chemistry, Faculty of Science, Mirpur University of Science and Technology (MUST), Allama Iqbal Road, 10250, Mirpur, AJK, Pakistan;2. Department of Chemistry, Khwaja Fareed University of Engineering & Information Technology, Rahim Yar Khan, 64200, Pakistan;3. Department of Physics, University of Sargodha, Sargodha, 40100, Pakistan;4. Department of Applied Chemistry, Government College University, Faisalabad, 38000, Pakistan;5. Department of Physics, College of Science, King Khalid University, Abha, 61413, P.O. Box 9004, Saudi Arabia;6. Department of Chemistry, College of Science, King Khalid University, Abha, 61413, P.O. Box 9004, Saudi Arabia;7. Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan;1. Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstrasse 48, 48149 Münster, Germany;2. Université de Lyon, Université Lyon 1, Faculté de Pharmacie-ISPB, EA 4446 Biomolécules Cancer et Chimiorésistances, SFR Santé Lyon-Est CNRS UMS3453-INSERM US7, 8 Avenue Rockefeller, F-69373 Lyon Cedex 8, France;1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People’s Republic of China;2. Department of Naval Health Service and Medical Equipment, Faculty of Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People’s Republic of China;3. International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People’s Republic of China;4. School of Pharmacy, East China University of Science & Technology, 130 Meilong Road, Shanghai 200237, People’s Republic of China;1. Graduate School in Neurosciences. University of Pecs, 12. Szigeti Str., 7624 Pecs, Hungary;2. Institute of Laboratory Medicine, University of Pecs, 13. Ifjusag St., 7624 Pecs, Hungary;3. Szentagothai Research Center, University of Pecs, 20. Ifjusag St., 7624 Pecs, Hungary;4. Markusovszky University Teaching Hospital, 5. Markusovszky St., 9700 Szombathely, Hungary;5. Institute of Neurology, University of Pecs, 2. Ret St., 7623 Pecs, Hungary |
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| Abstract: | Mithramycin is an inhibitor of the binding of the Sp-family transcription factor to the GC box. Many studies show that mithramycin may reduce the expression of many oncogenes by inhibiting the mRNA and protein synthesis and it has been used as an antibiotic chemotherapy drug for a long time. Recently, Eps8 (EGFR pathway substrate 8) has been revealed to be a novel proto-oncogene related to cellular transformation, Rac activation and actin barbed-end-capping activity. Therefore, the aim of this study was to verify whether Eps8 might be regulated by mithramycin. Results showed that mithramycin could reduce the mRNA and protein levels of Eps8 in dose- and time-dependent manners in several cancer cell lines. Furthermore, cell growth and migration ability were also reduced significantly by mithramycin treatment. Since Src is a well-known Eps8 activity enhancer, a v-Src transfected IV5 cell line was subjected to mithramycin treatment and then analyzed to show that Src expression was unable to restore the mithramycin-induced decrease in Eps8 expression, cell growth, and migration ability. To further confirm the above mentioned results, the expression of Eps8 was eliminated by a transient transfection with siRNA and subsequent analysis showed that silencing of Eps8 might also lead to a reduced growth and migration ability of cancer cells. These findings suggested that Eps8 was involved in the regulation of growth and motility of cancer cells and mithramycin might exert its anticancer ability via a pathway involving the downregulation of Eps8. |
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